The present invention relates to measurement systems and methods, and, more particularly, to a system and method providing for increased temporal peak-shape resolution in a mass spectrometer.
A primary objective of the present invention is to provide a strategy which optimizes the scan cycle time for a monotonically scanning instrument for a given range and accuracy. While the invention has particular applicability to mass spectrometry in conjunction with gas chromatography, the invention applies to other applications with similar considerations.
Mass spectrometry is a method of analyzing a gaseous sample by ionizing the constituent molecular components and separating these components according to mass-to-charge ratios. Generally, mass spectrometers include mass filters which use electric or magnetic fields to filter out all but a selected mass-to-charge ratio at a collector.
At any given instant, a mass spectrometer detects only molecules with the mass-to-charge ratio determined by the applied field. A complete mass spectrum for a sample is obtained by varying the field so that molecules with different mass-to-charge ratios are detected at different times. The collector output can be plotted against mass-to-charge ratio.
Mass spectrometers can be used in applications such as gas chromatography in which scanning speed is critical. Gas chromatography usually involves the separation of gaseous mobile phase sample components passed over a stationary phase mesh. Different sample components are retained to different degrees, causing them to elute at different times. Upon arrival of at the chromatograph's effluent end, they are introduced into a mass spectrometer.
For even minimal spectral quality of the resulting gas chromatogram, the mass spectrometer must perform two complete scans per chromatographic component peak. Characterizing chromatographic peak shapes requires more than two complete scans per component peak; four to seven scans are usually adequate. Where chromatographic peaks are unresolved, i.e., elute during overlapping intervals, even greater numbers of mass spectral scans are required to permit reliable mathematical deconvolution of the chromatogram.
Higher frequency cycling can be achieved by compromising one or more alternative performance criteria. One can reduce the mass range of the spectrometer; scan a given range with grosser steps while reducing the selectivity of the mass filter at the cost of mass resolution; or spend less time per measurement, with a concomitant loss in signal-to-noise ratio, and, therefore, accuracy.
In practice, improved cycling frequency without comparable tradeoffs in range, mass resolution and accuracy is achievable due to the fact that most mass spectra are primarily empty. For example, a typical sample might be represented by detections at 20-100 masses with a typical spectrometer range of 50-800 daltons. (A "dalton" is one-twelfth the mass of the common carbon isotope C.sup.12, practically equivalent to one atomic mass unit). Accordingly, the objective of achieving higher cycling frequency can be attacked with strategies for eliminating the waste involved as a spectrometer carefully measures nothing.
In the absence of such a strategy, an illustrative mass spectrometer might scan from 800 daltons to 50 daltons in one-tenth dalton decrements at 800 daltons per second, yielding a 1 Hz cycle time, or 1 second temporal resolution. By way of contrast, a simple dual-mode, survey/measurement, scan strategy precedes each normal measurement scan with a ten times faster survey scan. The low resolution survey scan suffices to exclude empty areas from the succeeding measurement scan. Thus, the measurement scan might only apply to about one third of the mass spectrum. Including the time for the survey scan and the intermediate backscan, such a strategy generally yields a significant improvement over a single-mode scan strategy.
A constraint on dual-mode strategies is that mass filters of mass spectrometers typically require stabilization prior to making a measurement. Abrupt changes in the mass being scanned incur considerable overhead in invalid measurements or stabilization time. The time required for instrument stabilization is minimized when scanning is gradual and monotonic. This is the typical approach used in single-mode measurement. Stabilization time requirements increase with upward scanning and with "hopping" between non-adjacent masses.
The performance of the simple dual-mode strategy described above is adversely affected by the requirement for stabilization. The larger and faster the leap, the greater the stabilization time required. Furthermore, once the survey is obtained, the skipping of blank spaces in the spectrum still consumes time. Thus, in the simple dual-mode strategy, blank areas consume scan time both during the survey scan and during measurement scan.
Other dual-mode strategies include a survey mode which switches to a measurement mode when a peak is detected. This generally involves backing up or jumping the mass filter, requiring additional stabilization time. Thus, while there are many strategies that afford an improvement over a single measurement mode, none of the available strategies is effectively optimized with respect to the stabilization requirements of mass filters. What is needed is a strategy which is well adapted to the stabilization requirements of mass spectrometers so as to optimize the scan cycling frequency.